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Oxidative stress in Phenylketonuria: future directions

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  • Published:
Journal of Inherited Metabolic Disease

Abstract

Phenylketonuria represents the most prevalent inborn error of amino acid metabolism. In early diagnosed patients adequate and continued dietary treatment results in a good neurologic outcome. Natural protein and phenylalanine-restricted diet, even if rich in fruits and vegetables, represents a serious risk for nutritional deficiencies, albeit universally accepted. In the last few years, a growing number of reports have been describing oxidative stress as a concern in phenylketonuric patients. The diet itself includes good sources of dietary antioxidants (phytochemicals, some vitamins and minerals) but also a risk factor for some deficiencies (selenium, zinc, ubiquinone-10 and L-carnitine). Additionally, the extreme stringency of the diet may impose a reduced synthesis of endogenous antioxidants (like ubiquinone-10 and glutathione). Furthermore, increased phenylalanine levels, and its metabolites, may enhance the endogenous synthesis of reactive species and free radicals and/or interfere with the endogenous synthesis of enzymatic antioxidants (like glutathione peroxidase). Therefore, oxidative stress will probably increase, mainly in late diagnosed patients or in those with bad metabolic control. Considering the known association between oxidative stress, obesity and cardiovascular disease, it seems advisable to look further to the impact of oxidative stress on body macromolecules and structures (like lipoprotein oxidation), especially in phenylketonuric patients with late diagnosis or bad metabolic control, in order to prevent future increased risks. Recommendations for PKU patient’s clinical follow-up improvement and educational goals are included.

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Abbreviations

CAT:

Catalase

GSH-px:

Glutathione peroxidase

HDL:

High density lipoprotein

LDL:

Low density lipoprotein

Phe:

L-Phenylalanine

PKU:

Phenylketonuria

PON:

Paraoxonase

PON1:

Paraoxonase 1

Q10:

Ubiquinone-10; coenzyme Q10

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RS:

Reactive species

Se:

Selenium

SOD:

Superoxide dismutase

TBARS:

Thiobarbituric acid-reactive species

Zn:

Zinc

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Acknowledgements

The authors gratefully acknowledge Fátima Santos, Isabel Azevedo and Tiago Martins for carefully reading the manuscript.

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Competing interest statement

Júlio César Rocha is a member of the Merck Serono European Nutritionist Expert Panel in Phenylketonuria.

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  1. Centro de Genética Médica Jacinto de Magalhães – INSA, IP, Praça Pedro Nunes, 88, 4099-028, Porto, Portugal

    Júlio César Rocha

  2. Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, 4200-319, Porto, Portugal

    Maria João Martins

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  1. Júlio César Rocha
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Correspondence to Júlio César Rocha.

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Rocha, J.C., Martins, M.J. Oxidative stress in Phenylketonuria: future directions. J Inherit Metab Dis 35, 381–398 (2012). https://doi.org/10.1007/s10545-011-9417-2

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